The role of AEG-1/MTDH/LYRIC in the pathogenesis of central nervous system disease

Adv Cancer Res. 2013:120:159-92. doi: 10.1016/B978-0-12-401676-7.00006-1.

Abstract

Astrocyte-elevated gene-1 (AEG-1/MTDH/LYRIC) is a potent oncogene that regulates key cellular processes underlying disease of the central nervous system (CNS). From its involvement in human immunodeficiency virus (HIV)-1 infection to its role in neurodegenerative disease and malignant brain tumors, AEG-1/MTDH/LYRIC facilitates cellular survival and proliferation through the control of a multitude of molecular signaling cascades. AEG-1/MTDH/LYRIC induction by HIV-1 and TNF highlights its importance in viral infection, and its incorporation into viral vesicles supports its potential role in active viral replication. Overexpression of AEG-1/MTDH/LYRIC in the brains of Huntington's disease patients suggests its function in neurodegenerative disease, and its association with genetic polymorphisms in large genome-wide association studies of migraine patients suggests a possible role in the pathogenesis of migraine headaches. In the field of cancer, AEG-1/MTDH/LYRIC promotes angiogenesis, migration, invasion, and enhanced tumor metabolism through key oncogenic signaling cascades. In response to external stress cues and cellular mechanisms to inhibit further growth, AEG-1/MTDH/LYRIC activates pathways that bypass cell checkpoints and potentiates signals to enhance survival and tumorigenesis. As an oncogene that promotes aberrant cellular processes within the CNS, AEG-1/MTDH/LYRIC represents an important therapeutic target for the treatment of neurological disease.

Keywords: AEG-1/MTDH/LYRIC; CNS; Cancer; Glioblastoma; HIV.

Publication types

  • Review

MeSH terms

  • Animals
  • Autophagy / physiology
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Cell Adhesion Molecules / physiology*
  • Central Nervous System / metabolism
  • Central Nervous System Diseases / diagnosis
  • Central Nervous System Diseases / etiology*
  • Central Nervous System Diseases / therapy
  • Drug Resistance, Neoplasm / genetics
  • Genetic Association Studies
  • Humans
  • Membrane Proteins
  • Neoplasm Invasiveness
  • RNA-Binding Proteins

Substances

  • Cell Adhesion Molecules
  • MTDH protein, human
  • Membrane Proteins
  • RNA-Binding Proteins